A new SEMA7A variant found in Native Americans with alloantibody

Area of Science:

• Immunohaematology
• Molecular Genetics
• Protein Polymorphism

Background:

• Semaphorin 7A (SEMA7A) carries John Milton Hagen (JMH) antigens, with roles in the nervous and immune systems.
• The function of SEMA7A on erythrocytes and its association with JMH antigens remain unclear.
• Limited cases of JMH status elucidation are referred to reference laboratories.

Purpose of the Study:

• To investigate the molecular basis of JMH diversity on erythrocytes.
• To identify polymorphisms in SEMA7A responsible for observed JMH variations.
• To characterize antibodies associated with JMH-negative red blood cells.

Main Methods:

• Analysis of seven blood samples with JMH1-negative compatible antibodies.
• Molecular sequencing of SEMA7A cDNA in Native American and Caucasian individuals.
• Production of soluble recombinant Sema7A proteins for antibody characterization via ELISA.

Main Results:

• A novel SEMA7A exon 9 polymorphism (G>T at position 1040) was identified in Native American samples.
• This polymorphism results in an amino acid change at position 347 (Arg to Leu).
• Native American plasma antibodies specifically recognized wild-type Sema7AArg347 but not the Sema7ALeu347 variant.

Conclusions:

• A new SEMA7A variant associated with JMH antigen diversity has been identified.
• The antibody found in Native American plasma is an alloantibody due to its specific recognition of the wild-type Sema7AArg347 protein.